A modified Williams airway intubator to assist fibreoptic intubation.
Explore the source record for details and available documents.
Equipment Design↗
Biomedical subjects
D C Chung
Publications and source records attributed to D C Chung.
Oncogenic ras induces gastrin gene expression in colon cancer.
BACKGROUND & AIMS: The expression of gastrin, as a tumor growth factor, is significantly increased in some colon cancers compared with the low levels found in normal mucosa. The aim of this study was to elucidate the transcriptional mechanisms of gastrin induction in colon cancer. METHODS: Gastrin messenger (mRNA) levels and K-ras genotype were determined in colon cancer cell lines and surgical specimens. Colon cancer cells were transfected with oncogenic ras expression vectors, and transcriptional activity was assayed with gastrin-luciferase reporter genes. RESULTS: Colon cancer cell lines and tissues with K-ras mutations all had significantly higher gastrin mRNA levels than those that were ras wild type. Treatment of several ras mutant cell lines with PD98059, an inhibitor of mitogen-activated protein kinase kinase, resulted in a decrease in endogenous gastrin mRNA levels. The effects of ras on gastrin expression appeared to be mediated through the gastrin promoter because transfection of oncogenic ras and activated raf expression vectors both induced gastrin-promoter, luciferase-reporter genes. The inductive effects of oncogenic ras could be blocked by the coexpression of dominant negative forms of raf and extracellular regulated kinase. CONCLUSIONS: Oncogenic ras induces gastrin gene expression through activation of the Raf-MEK-ERK signal transduction pathway.
Calcium-Calmodulin-Dependent Protein Kinases↗
Molecular prognostic markers and colorectal cancer: the search goes on.
Explore the source record for details and available documents.
Chromosomes, Human, Pair 18↗
A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications.
The molecular pathogenesis of pancreatic endocrine tumors is largely unknown. Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome. We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL. Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors. Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease.
Adolescent↗
Analysis of the retinoblastoma tumour suppressor gene in pancreatic endocrine tumours.
OBJECTIVES: The molecular pathogenesis of human pancreatic endocrine tumours (PETs) is largely unknown. One attractive candidate gene for involvement in pancreatic endocrine neoplasia is the retinoblastoma (Rb) tumour suppressor gene. A deletion of the Rb gene was recently described in a human insulinoma. In addition, mice harbouring a null mutation in the Rb gene bred with p53 mutant mice develop pancreatic endocrine tumours. Therefore, we sought to determine the role that allelic loss of Rb may play in a large series of human pancreatic endocrine tumours. PATIENTS AND MEASUREMENTS: 46 pancreatic endocrine tumours were obtained from 41 patients. Utilizing genomic DNA isolated from the tumour samples and control normal cells, 2 highly polymorphic microsatellite loci (D13S153 and Rb 1.20) located within the Rb gene were PCR amplified and examined for loss of heterozygosity. RESULTS: 2 patients were homozygous at both loci and thus uninformative. The remaining 39 had informative markers at one or both of these loci, and none of the tumours from these patients demonstrated allelic loss of Rb. CONCLUSIONS: In tumours in which Rb inactivation is pathogenetically important, somatic loss of one Rb allele commonly accompanies a point mutation or microdeletion within the other allele. Thus, the absence of demonstrable allelic loss in this large series strongly suggests that Rb gene inactivation is not frequently involved in the pathogenesis of human pancreatic endocrine tumours.
Adenoma, Islet Cell↗
A dynamic model of ventricular interaction and pericardial influence.
A mathematical model describing the dynamic interaction between the left and the right ventricle over the complete cardiac cycle is presented. The pericardium-bound left and right ventricles are represented as two coupled chambers consisting of the left and right free walls and the interventricular septum. Time-varying pressure-volume relationships characterize the component compliances, and the interaction of these components produces the globally observed ventricular pump properties (total chamber pressure and volume). The model 1) permits the simulation of passive (diastolic) and active (systolic) ventricular interaction, 2) provides temporal profiles of hemodynamic variables (e.g., ventricular pressures, volumes, and flow) that agree well with reported observations, and 3) can be used to examine the effect of the pericardium on ventricular interaction and ventricular mechanics. It can be reduced to equivalency with models previously reported by invoking simplifying assumptions. Furthermore, model-generated "dynamic interaction gains" are employed to quantify the mode and degree of ventricular interaction. The model also yields qualitative predictions of septal and free wall displacements similar to those detected experimentally via M-mode echocardiography. Such analogies may be extended easily to the study of pathophysiological states via appropriate modifications to 1) the pressure-volume characteristics of the component walls (and/or pericardium) and/or 2) the specific time course of activation of the ventricular free wall or the septum. A limited number of examples are included to demonstrate the utility of the model, which may be used as an adjunct to new experimental investigations into ventricular interaction.
Blood Volume↗
Results of functioning free muscle transplantation for elbow flexion.
Thirty-eight patients underwent functioning free muscle transplantation for restoration of elbow flexion. Thirty-five patients had sustained brachial plexus injury and 3 had traumatic loss of the biceps muscle. The gracilis muscle was used in 37 patients and the rectus femoris muscle in 4. The transferred muscle was reinnervated by the musculocutaneous (n = 3), intercostal (n = 31), and spinal accessory (n = 4) nerves. Results were assessed by the Medical Research Council grading system and success was defined as a muscle strength of M4. Reinnervation with the musculocutaneous nerve resulted in success in all cases (n = 3) within 1 year. Success was obtained in 78% of patients following transfer of 3 intercostal nerves (n = 23) with recovery in an average of 2 years. Using the spinal accessory nerve (n = 4), strength of only M2+ was achieved, probably on account of the need for interposition nerve grafts in those cases.
Adolescent↗
Adenovirus-mediated gene transfer of ornithine aminotransferase in cultured human retinal pigment epithelium.
PURPOSE: To evaluate the efficacy of adenovirus mediated transfer of ornithine delta-aminotransferase (OAT) into human retinal pigment epithelial (RPE) cells. METHODS: Adenovirus-mediated gene transfer into primary cultures of human RPE was evaluated by measurement of enzyme activity in whole cell extracts and by Western blot analysis. To assess mitochondrial integrity, succinate dehydrogenase activity was measured in transduced RPE cells. Expression of adenovirus early genes was evaluated using reverse transcription-polymerase chain reaction. RESULTS: OAT activity, which was 65 nmol/mg.hour in untransduced cells, could be increased to levels in excess of 20,000 nmol/mg.hour using an adenovirus vector carrying the OAT cDNA. There was, however, a significant reduction in succinate dehydrogenase activity associated with OAT activity greater than 12,000 nmol/mg.hour. Transduced human RPE displayed an altered morphology that appears to be a response to the vector because similar changes could be induced by an adenovirus vector that does not carry the OAT cDNA. Adenovirus early gene expression was detected in transduced RPE. CONCLUSIONS: This study represents a first step in the development of intraocular gene replacement therapy for the treatment of gyrate atrophy. The authors demonstrate that adenovirus is an efficient vehicle for the delivery of OAT into human RPE and that RPE will tolerate greater than a 150-fold increase in OAT-specific activity. Evidence for disruption of mitochondria when OAT activity exceeds 12,000 nmol/mg.hour and vector-induced toxicity indicate that more controlled transgene expression and refinement of the vector systems is needed.
Adenoviruses, Human↗
Mutually exclusive interactions between factors binding to adjacent Sp1 and AT-rich elements regulate gastrin gene transcription in insulinoma cells.
The gastrin gene is transiently expressed in fetal pancreatic islets during islet neogenesis but then switched off after birth when islet cells become fully differentiated. Previous studies identified a cis-regulatory sequence between -109 and -75 in the human gastrin promoter which binds islet cell-specific activators and a nonspecific repressor and thus may act as a molecular switch. The present study identified another cis-regulatory sequence (-163ACACTAAATGAAAGGGCGGGGCAG-140) which bound two islet nuclear proteins in a mutually exclusive manner, as defined by gel shift competition, methylation interference, and DNase I foot-printing assays. The general transactivator Sp1 recognized the downstream GGGCGGGG sequence, but Sp1 binding was prevented when another islet factor bound to the adjacent AT-rich sequence (CTAAATGA). This gastrin AT-rich element is nearly identical to the binding site (ATAAATGA) for the islet-specific transcription factor beta TF-1. However, the gastrin AT-binding factor appeared to differ from beta TF-1 in its gel mobility shift pattern. Transfections of rat insulinoma cells revealed that mutations which blocked binding to the AT-rich element but allowed Sp1 binding up-regulated transcriptional activity. These results suggest that the gastrin AT-binding factor blocks transactivation by Sp1 and may have a role in the repression of gastrin transcription seen at the end of islet differentiation.
Adenine↗
DNA mismatch repair and cancer.
The genetic basis of cancer involves certain classes of genes, particularly oncogenes, tumor-suppressor genes, and DNA mismatch repair genes. Originally identified in bacteria and yeast, the human homologues of DNA mismatch repair genes have been implicated in the pathogenesis of the hereditary nonpolyposis colorectal cancer syndromes, as well as a variety of different sporadic cancers. An appreciation of their role in cancer is predicated on an understanding of their function in the processes of DNA repair. This article reviews the recent developments and advances in the biology of the human DNA mismatch repair genes and their involvement in the pathogenesis of cancer.
Colonic Neoplasms↗
Anaesthesia for three-stage thoracoscopic oesophagectomy: an initial experience.
We report our experience in the anaesthetic management of five patients undergoing three-stage thoracoscopic oesophagectomy. One patient required conversion to open thoracotomy because of extensive pleural adhesions. The other four patients, aged between 68 and 78, were all chronic smokers with mid-oesophageal squamous cell carcinoma. The duration of thoracoscopic surgery (and obligatory one-lung ventilation) ranged from 2.5 to 4 hours with total surgical time ranging from 7.5 to 9.5 hours. Anaesthetic considerations included the use of one-lung ventilation to provide surgical access, the cardiorespiratory effects of capnothorax, difficulties in assessing surgical blood loss during thoracoscopic dissection, crowding in the operating room with limitation of access to the patient and the risk of intraoperative dislodgement of the endobronchial tube. Postoperative pulmonary complications were not decreased in our patients despite the avoidance of thoracotomy. The thoracoscopic technique might contribute to pulmonary complications because of prolonged thoracoscopic dissection and unintentional pulmonary injuries. The concept of minimally invasive surgery needs further evaluation when the technique is applied in extensive procedures such as oesophagectomy.
Aged↗
Validation of arterial oxygen saturation measurements in utero using pulse oximetry.
The noninvasive measurement of fetal arterial oxygen saturation using pulse oximetry could be of potential use in assessing fetal well-being in utero during labor. In this study, the accuracy and technical feasibility of reflectance pulse oximetry in utero was evaluated in acutely instrumented fetal sheep using a specially designed sensor. Following recalibration of the analysis algorithms, fetal arterial saturation could be measured by pulse oximetry in utero. Arterial oxygenation measurements obtained using pulse oximetry correlated well with simultaneous in vitro measurements over the range of 6 to 81%. We conclude that in utero pulse oximetry is technically feasible, appears useful and accurate, and merits further evaluation.
Algorithms↗
A very small dose of suxamethonium relieves laryngospasm.
Intravenous suxamethonium, in a dose as small as 0.1 mg.kg-1, has been found to be reliable in the treatment of laryngeal spasm. Three episodes of vocal cord spasm observed during direct laryngoscopy were relieved by this dose of suxamethonium.
Aged↗
Awake endobronchial intubation.
Explore the source record for details and available documents.
Administration, Topical↗
Partially paralyzed: a personal experience.
Explore the source record for details and available documents.
Atracurium↗
Do fetal pulse oximetry readings at delivery correlate with cord blood oxygenation and acidaemia?
OBJECTIVE: To assess the accuracy of a pulse oximeter in the fetus. DESIGN: A prospective descriptive study, comparing oxygenation and acidaemia of cord blood with oxygen saturation in the arteries of the fetal scalp measured by a pulse oximeter just before delivery. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: The labour ward in a teaching hospital. SUBJECTS: Thirty seven Caucasian fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURE: Fetal pulse oximetry reading shortly before birth, umbilical cord oxygenation and pH, and Apgar scores. RESULTS: Data of sufficient quality were obtained from 28 fetuses. There was a highly significant correlation between pulse oximetry reading and umbilical vein oxygen saturation r = 0.59, P = < 0.001). There was also a significant correlation between the pulse oximeter reading and cord blood pH (vein: r = 0.57, P = 0.002, artery: r = 0.63, P = 0.001). Apgar scores were not related to the oximetry results. CONCLUSION: Pulse oximetry readings reflect fetal oxygenation at birth.
Apgar Score↗
Transmission of hepatitis B virus infection by iatrogenic intramuscular injections in an endemic area.
The authors followed 95 people from the general and aboriginal population of Taiwan, aged 5 to 69 years for two years. All of subjects studied were susceptible to hepatitis B virus (HBV) infection. In all, 56 of the 95 persons received iatrogenic intramuscular (IM) injections, and 28 of the 95 became newly infected with HBV during the study period. The relative risk of being infected with HBV was higher in people who received an IM injection (IRR = 5.8, 95% CI 1.9-17.9) than in those who did not. New HBV infections were found to correlate significantly with the frequency of injections (Ptrend less than 0.000) and therefore, we concluded that (A) intramuscular injections played an important role in horizontal transmission of HBV, particularly among Aborigines and that (B) the infection was transmitted via inadequately sterilized syringes used for iatrogenic IM injections in a community in which the hepatitis B virus was prevalent and IM injections were common.
Adolescent↗
Intramuscular-injection-associated gluteal fibrotic contracture and hepatitis B virus infection among school children.
A case control study was carried out to determine the exposure factors of gluteal fibrotic contracture (GFC). Sixty two school children were taken as the case group and were matched for sex, age and village of residence with 62 of their classmates constituting the control group. It was found that all 62 members of the case group had received intramuscular (IM) injections at some time prior to the onset of GFC, while only 57 of the control group had received IM injections. This difference is a statistically significant (p = 0.029). Injection sites on both buttocks were higher in the case group than among the controls. The odds ratio for the prevalence of hepatitis B virus infection (HBV) in the case group as compared to the control group was 3.0 (95% CI 1.1-7.8). A trend correlation was found between the annual frequency of IM injection, GFC and HBV infection. We concluded that IM injections played an important role in GFC and added to the risk of HBV infection, because they had been administered by improperly sterilized reusable syringes in an area where both GFC and HBV infections were prevalent and IM injection was common.
Adolescent↗